SCI 발표논문

2017년 269편

2092017

제1저자 지명진 · 교신저자 김정희

, , , , , , ,
Best candidates for dopamine agonist withdrawal in patients with prolactinomas.
Pituitary. 2017;20(5):578-584.

Abstract
PURPOSE Dopamine agonist (DA) therapy is recommended as the first-line treatment for prolactinomas. However, it requires long treatment duration, and a high recurrence rate after DA withdrawal has been reported. We aimed to elucidate the predictors for long-term remission following DA withdrawal and propose the best candidates who can achieve complete remission after DA withdrawal.
METHODS In a retrospective cohort study, we included 89 patients with prolactinoma who have withdrawn DAs with normal prolactin (PRL) levels at Seoul National University Hospital, from 2000 to 2016. Patient's data were retrieved from the electronic medical records.
RESULTS The median age and median treatment duration of the study patients were 33 (15-73) years and 69.5 (8.3-277.4) months, respectively. The recurrence rate after drug withdrawal was 57.3% during the 23.9 (3.0-176.8) month follow-up period. Age, gender, baseline PRL level, and baseline maximum tumor diameter were similar between the remission and recurrence group. In the Cox-proportional hazard model analysis, the significant predictors for remission were nadir PRL level of <1 ng/dL (hazard ratio [95% confidence interval] = 0.37 [0.18-0.74]), invisible tumors on magnetic resonance imaging (MRI) (0.42 [0.24-0.74]), and treatment duration of >72 months (0.54 [0.30-0.96]). Of the subjects who met all the three criteria, 66.7% achieved long-term remission.
CONCLUSIONS Patients who have no tumor visible on MRI, have a nadir PRL level <1 ng/dL during drug treatment, and received drug treatment for >6 years may be the best candidates for DA withdrawal.
PubMed IF 3.8 내분비대사내과
2082017

제1저자 방영주 · 교신저자 방영주, Markus Moehler

, , , , , , , , ,
Efficacy of Sequential Ipilimumab Monotherapy versus Best Supportive Care for Unresectable Locally Advanced/Metastatic Gastric or Gastroesophageal Junction Cancer.
Clin Cancer Res. 2017;23(19):5671-5678.

Abstract
Purpose: Ipilimumab, a monoclonal antibody that blocks cytotoxic T-lymphocyte-associated protein-4 interactions, enhances T-cell activation and promotes tumor immunity. This phase II study evaluated the safety and efficacy of ipilimumab monotherapy versus best supportive care (BSC) among patients with advanced/metastatic gastric or gastroesophageal junction cancer who achieved at least stable disease with first-line chemotherapy.Experimental Design: Eligible patients were randomized to ipilimumab 10 mg/kg every 3 weeks for four doses, then 10 mg/kg every 12 weeks for up to 3 years, or BSC, which could include continuation of fluoropyrimidine until progression or toxicity. The primary endpoint was immune-related progression-free survival (irPFS); secondary endpoints included PFS by modified World Health Organization criteria and overall survival (OS).Results: Of 143 patients screened, 57 were randomized to each arm. irPFS with ipilimumab versus BSC was not improved [2.92 months, 95% confidence interval (CI), 1.61-5.16 vs. 4.90 months, 95% CI, 3.45-6.54, HR = 1.44; 80% CI, 1.09-1.91; P = 0.097], resulting in study cessation. At study closeout, which occurred 8 months after the interim analysis, the median OS durations were 12.7 months (95% CI, 10.5-18.9) and 12.1 months (95% CI, 9.3-not estimable), respectively. Grade 3/4 treatment-related adverse events occurred in 23% of ipilimumab-treated patients, in whom diarrhea (9%) and fatigue (5%) were most frequent, and in 9% of active BSC-treated patients.Conclusions: Although ipilimumab at 10 mg/kg was manageable, it did not improve irPFS versus BSC. However, comparable median OS of approximately 1 year and a favorable safety profile support the investigation of ipilimumab in combination with other therapies for advanced gastric cancer. Clin Cancer Res; 23(19); 5671-8. ©2017 AACR.
PubMed IF 10.9 혈액종양내과
2072017

제1저자 민세희 · 교신저자 임수

, , , , , , , ,
Association of angiotensin-II levels with albuminuria in subjects with normal glucose metabolism, prediabetes, and type 2 diabetes mellitus.
J Diabetes Complications. 2017;31(10):1499-1505.

Abstract
OBJECTIVES The relationship between the renin-angiotensin system (RAS) and diabetes has been studied for many years. However, studies that assessed RAS components comprehensively were limited. We hypothesized that serum RAS components, especially the effector peptide angiotensin-II, might be closely associated with glucose metabolism status and diabetic complications.
METHODS We investigated the association of individual RAS component with albuminuria in 407 subjects with normal glucose metabolism (NGM), prediabetes, or type 2 diabetes mellitus (T2DM). Anthropometric and biochemical parameters, including glucose homeostasis, albuminuria, and RAS-related parameters such as plasma renin activity (PRA), aldosterone, angiotensin-converting enzyme (ACE), and angiotensin-II levels, were measured.
RESULTS The mean±standard deviation (SD) age and body mass index were 57.1±11.1years and 24.7±3.3kg/m², respectively. There were 54 subjects with NGM, 102 with prediabetes, and 251 with T2DM. The mean±SD angiotensin-II levels in these groups were 9.32±6.89, 12.89±10.39, and 17.00±15.28pg/mL, and the respective urinary albumin-to-creatinine ratios (ACRs) were 8.1±5.3, 13.3±17.3, and 30.7±51.9mg/g, which were significantly different among the groups. The serum angiotensin-II levels were correlated with levels of PRA, insulin resistance, C-reactive protein, and urinary ACR. Among RAS-related parameters, only the angiotensin-II level was significantly associated with urinary ACR after adjusting for relevant risk factors.
CONCLUSIONS Angiotensin-II may play an important role in the development of albuminuria, particularly in subjects with impaired glucose metabolism.
PubMed IF 3.2 내분비대사내과
2062017

제1저자 황성욱, 김지현 · 교신저자 임종필

, , , , , , , , , , , ,
Influence of age at diagnosis on the clinical characteristics of Crohn's disease in Korea: Results from the CONNECT study.
J Gastroenterol Hepatol. 2017;32(10):1716-1722.

Abstract
BACKGROUND AND AIM The present study evaluated the clinical characteristics of Korean patients with Crohn's disease (CD) according to their age at diagnosis in a nationwide multicenter cohort study.
METHODS A total of 1224 patients diagnosed with CD between 1982 and 2008 in 32 hospitals were included, and age at diagnosis was categorized as ≤ 16 (G1), 17-40 (G2), 41-59 (G3) and ≥ 60 (G4) years old. The baseline characteristics, medication, and intestinal resection were compared according to the age at diagnosis.
RESULTS The number of patients in each age group was 155 (G1; 12.7%), 919 (G2; 75.1%), 120 (G3; 9.8%), and 30 (G4; 2.5%). The frequencies of ileocolonic disease in the late adult onset and elderly onset groups were lower than those in the other groups (P < 0.001). The cumulative probabilities of thiopurine and anti-tumor necrosis factor use in late adult onset and elderly onset groups were significantly reduced compared with those of the other groups (P < 0.01). However, the risk of the first intestinal resection was not different among the age groups. The ileal location (hazard ratio [HR]: 1.59; 95% confidence interval [CI]: 1.11-2.27), complicated behavior (HR: 3.35; 95% CI: 2.63-4.27), and early thiopurine use (HR: 0.27; 95% CI: 0.17-0.43) were associated with the first intestinal resection, whereas the age at diagnosis was not a risk factor.
CONCLUSIONS Elderly onset CD may be related to favorable outcomes in Korea. Thus, the heterogeneity of this disease should be considered when developing a tailored strategy for the treatment of CD.
PubMed IF 3.5 소화기내과
2052017

제1저자 김세훈, 강시혁 · 교신저자 연태진

, , , , , , , , , , , , , , , , , ,
Relation between secondhand smoke exposure and cardiovascular risk factors in never smokers.
J Hypertens. 2017;35(10):1976-1982.

Abstract
OBJECTIVE Secondhand smoke exposure (SHSE) in nonsmokers has been associated with premature cardiovascular mortality and ischemic heart disease. We conducted a cross-sectional, population-based study evaluating the relationship between SHSE, measured by subjective and objective methods, and conventional cardiovascular risks such as blood pressure, lipid profiles, and fasting glucose.
METHODS We extracted information on 7376 healthy adults who had never smoked, for whom there were available urine cotinine levels, from the Korea National Health and Nutrition Examination Survey 2008-2011. SHSE was defined using self-report questionnaires and urine cotinine levels. The main outcomes included SBP and DBP, serum lipid profiles, and fasting glucose.
RESULTS The mean age of the study population was 45.4 ± 0.4 years and 75.2% were women. Self-reported SHSE had no significant association with study outcomes except for DBP, which had marginally positive relationships (P = 0.060). Unadjusted analysis showed higher cotinine levels were associated with lower SBP, total cholesterol, LDL cholesterol, and triglyceride. All associations lost statistical significance after multivariable adjustment. Fasting glucose had a positive relationship with urine cotinine in quartiles but not with logarithm-transformed cotinine.
CONCLUSION Although SHSE is associated with increased risk of cardiovascular mortality and morbidity, we did not find any consistent relationship among SHSE and blood pressure, lipid, or fasting glucose levels in this cross-sectional study. Using objective measurements of urine cotinine did not alter this relationship. Further long-term prospective studies are needed to evaluate the effect of SHSE as a cardiovascular risk factor.
PubMed IF 5.6 순환기내과
2042017

제1저자 이소령, 채인호 · 교신저자 김효수, 김상현

, , , , ,
Predictors of candesartan's effect on vascular reactivity in patients with coronary artery disease.
Cardiovasc Ther. 2017;35(5):e12291.

Abstract
INTRODUCTION AND AIMS Endothelial dysfunction and arterial stiffness have a prognostic value on adverse long-term outcomes in coronary artery disease (CAD) patients. We evaluated the efficacy on vascular reactivity of candesartan and analyzed predictors to control the candesartan's effect on vascular reactivity in CAD patients.
METHOD Patients were prospectively enrolled and prescribed candesartan for 6 months. The effect on vascular reactivity was evaluated by the change in flow-mediated dilation (FMD) and pulse wave velocity (PWV).
RESULTS A total of 124 patients completed the study. The better responder in FMD change (≥1.3%) showed significantly lower baseline FMD than the poor responder (P < .001). In receiver operating characteristic analysis, baseline FMD 7.5% showed optimal predictive value (sensitivity 79%, specificity 79%) for predicting better responder. The baseline endothelial dysfunction (FMD <7.5%) was the only significant predictor of the better responder to candesartan. The better responder in PWV change (≤-100 cm/s) showed greater blood pressure lowering and significantly higher baseline PWV than the poor responder (both P < .05). The poor responder in both FMD and PWV showed a higher prevalence of previous myocardial infarction (38.7% vs 17.2%, P = .013).
CONCLUSION The candesartan's effect on vascular reactivity is more pronounced in patients with more severe endothelial dysfunction and arterial stiffness. Poor responders on both FMD and PWV showed higher prevalence of previous myocardial infarction.
PubMed IF 2.8 순환기내과
2032017

제1저자 임수 · 교신저자 최동섭

, , , , , , , , , , ,
Effects of Lobeglitazone, a Novel Thiazolidinedione, on Bone Mineral Density in Patients with Type 2 Diabetes Mellitus over 52 Weeks.
Diabetes Metab J. 2017;41(5):377-385.

Abstract
BACKGROUND The aim of this multicenter, randomized, double-blind study was to examine the effect of lobeglitazone, a novel thiazolidinedione, on the changes in bone mineral density (BMD) in patients with type 2 diabetes mellitus.
METHODS A 24-week, double-blinded phase was followed by a 28-week, open-label phase, in which the placebo group also started to receive lobeglitazone. A total of 170 patients aged 34 to 76 years were randomly assigned in a 2:1 ratio to receive lobeglitazone 0.5 mg or a matching placebo orally, once daily. BMD was assessed using dual-energy X-ray absorptiometry at week 24 and at the end of the study (week 52).
RESULTS During the double-blinded phase, the femur neck BMD showed decreasing patterns in both groups, without statistical significance (-0.85%±0.36% and -0.78%±0.46% in the lobeglitazone and placebo groups, respectively). The treatment difference between the groups was 0.07%, which was also not statistically significant. Further, minimal, nonsignificant decreases were observed in both groups in the total hip BMD compared to values at baseline, and these differences also did not significantly differ between the groups. During the open-label phase, the BMD was further decreased, but not significantly, by -0.32% at the femur neck and by -0.60% at the total hip in the lobeglitazone group, and these changes did not significantly differ compared with the original placebo group switched to lobeglitazone.
CONCLUSION Our results indicate that treatment with lobeglitazone 0.5 mg over 52 weeks showed no detrimental effect on the BMD compared to the placebo.
PubMed IF 8.2 내분비대사내과
2022017

제1저자 서경진 · 교신저자 김지현

, , , , , , , , , , , , , , ,
Bilateral Salpingo-oophorectomy Compared to Gonadotropin-Releasing Hormone Agonists in Premenopausal Hormone Receptor-Positive Metastatic Breast Cancer Patients Treated with Aromatase Inhibitors.
Cancer Res Treat. 2017;49(4):1153-1163.

Abstract
PURPOSE Although combining aromatase inhibitors (AI) with gonadotropin-releasing hormone agonists (GnRHa) is becoming more common, it is still not clear if GnRHa is as effective as bilateral salpingo-oophorectomy (BSO).
MATERIALS AND METHODS We retrospectively analyzed data of 66 premenopausal patients with hormone receptor- positive, human epidermal growth factor receptor 2-negative recurrent and metastatic breast cancer who had been treated with AIs in combination with GnRHa or BSO between 2002 and 2015.
RESULTS The median patient age was 44 years. Overall, 24 (36%) received BSO and 42 (64%) received GnRHa. The clinical benefit rate was higher in the BSO group than in the GnRHa group (88% vs. 69%, p=0.092). Median progression-free survival (PFS) was longer in the BSO group, although statistical significance was not reached (17.2 months vs. 13.3 months, p=0.245). When propensity score matching was performed, the median PFS was 17.2 months for the BSO group and 8.2 months for the GnRHa group (p=0.137). Multivariate analyses revealed that the luminal B subtype (hazard ratio, 1.67; 95% confidence interval [CI], 1.08 to 2.60; p=0.022) and later-line treatment (≥ third line vs. first line; hazard ratio, 3.24; 95% CI, 1.59 to 6.59; p=0.001) were independent predictive factors for a shorter PFS. Incomplete ovarian suppression was observed in a subset of GnRHa-treated patients whose disease showed progression, with E2 levels higher than 21 pg/mL.
CONCLUSION Both BSO and GnRHa were found to be effective in our AI-treated premenopausal metastatic breast cancer patient cohort. However, further studies in larger populations are needed to determine if BSO is superior to GnRHa.
PubMed IF 4.2 혈액종양내과
2012017

제1저자 곽낙원 · 교신저자 임재준

, , , , ,
Treatment Outcomes of Mycobacterium avium Complex Lung Disease: A Systematic Review and Meta-analysis.
Clin Infect Dis. 2017;65(7):1077-1084.

Abstract
BACKGROUND The advent of macrolides has led to therapeutic advances in the treatment of Mycobacterium avium complex lung disease (MAC-LD). The aim of this study was to elucidate the treatment outcomes of macrolide-containing regimens.
METHODS We performed a systematic review and meta-analysis of published studies reporting treatment outcomes of macrolide-containing regimens for MAC-LD using the Medline, Embase, and Cochrane Library databases through 31 July 2016. The rates of treatment success, default from treatment, and adverse events of macrolide-containing regimens were assessed. Treatment success was defined as either 12 months of sustained culture negativity while on therapy or achievement of culture conversion and completion of the planned treatment without relapse.
RESULTS In total, 16 studies involving 1462 patients were included. The rate of treatment success was 60.0% (95% confidence interval [CI], 55.1%-64.8%). The proportion of patients who defaulted from the treatment was 16.0% (95% CI, 12.3%-19.7%). When a thrice-weekly dosing schedule was available, the default rate was 12.0% (95% CI, 8.9%-15.0%). Adverse events necessitating treatment discontinuation or dosage modification of macrolides were observed in 6.4% of patients (95% CI, 3.2%-9.5%), and decreased auditory acuity was the most common adverse event.
CONCLUSIONS Treatment outcomes of macrolide-containing regimens are relatively poor in terms of both the treatment success and default rates. The default rate could be reduced if a thrice-weekly dosing schedule is available. Clinicians should be aware of decreased auditory function as the most common adverse event associated with macrolide-containing regimens.
PubMed IF 8.3 호흡기내과
2002017

제1저자 박한기 · 교신저자 강혜련

, , , , ,
Epidemiology of drug-induced anaphylaxis in a tertiary hospital in Korea.
Allergol Int. 2017;66(4):557-562.

Abstract
BACKGROUND Epidemiology and risk factors of drug-induced anaphylaxis are difficult to estimate due to lack of confirmative diagnosis and under reporting. Here we report the current state of drug-induced anaphylaxis in Korea based on an in-hospital pharmacovigilance database in a tertiary hospital.
METHODS This study is a retrospective analysis of drug-induced anaphylaxis, reported to an in-hospital pharmacovigilance center in Seoul National University Hospital from June 2009 to May 2013. Anaphylaxis occurred in patients under 18 years of age or developed by medications administered from outside pharmacies or hospitals were excluded. We assessed causative drug, incidence per use of each drug and risk factors of fatal anaphylactic shock.
RESULTS A total of 152 in-hospital drug-induced anaphylaxis cases were reported during the study period. The single most frequently reported drug was platinum compound and the incidence of anaphylaxis and anaphylactic shock in platinum compounds users was 2.84 and 1.39 per 1000 patients use. Risk factors of anaphylactic shock among total anaphylaxis cases were identified as older age ≥70 years [Odd's ratio (OR), 5.86; 95% confidence interval (CI), 1.70-20.14]. The use of iodinated contrast media (OR, 6.19; 95% CI, 1.87-20.53) and aminosteroid neuromuscular blocking agent (NMBA) (OR, 12.82; 95% CI, 1.50-109.92) were also a risk factor for the development of anaphylactic shock.
CONCLUSIONS Platinum compounds are the most commonly reported causative agents of in-hospital drug-induced anaphylaxis. Older age ≥70 years and drugs such as iodinated contrast media and aminosteroid NMBA are related with high risk of anaphylactic shock.
PubMed IF 6.2 알레르기내과
1992017

제1저자 박재용 · 교신저자 김상균

, , , , , , , ,
Risk factors for early metachronous tumor development after endoscopic resection for early gastric cancer.
PLoS One. 2017;12(9):e0185501.

Abstract
BACKGROUND Metachronous gastric tumor (MGT) is one of major concerns after endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). Optimal follow-up strategy has not been yet well-established. The aim of this study was to identify the different clinical features of the patients according to the time interval to development of MGT.
METHODS Among 1,780 consecutive patients with EGC who underwent ESD between 2005 and 2014, 115 patients with MGT were retrospectively reviewed. MGT was defined as secondary gastric cancer or dysplasia detected > 1 year after initial ESD. Clinicopathological factors associated with early development of MGT were evaluated.
RESULTS The median interval to development of MGT was 37 months. In univariate analysis, the median interval to MGT was shorter if EGC lesion was non-elevated type (39.4 vs 57.0 months, p = 0.011), or synchronous primary lesion was absent (39.8 vs 51.4 months, p = 0.050). In multivariate Cox's proportional hazards analysis, the hazard ratios for early occurrence of MGT were 1.966 (95% CI: 1.141-3.386, p = 0.015) and 1.911 (95% CI: 1.163-3.141, p = 0.011), respectively. There was no significant difference in overall survival after diagnosis of MGT between the early occurrence group and the late occurrence group.
CONCLUSIONS Non-elevated gross type and absence of synchronous gastric tumor were independent risk factors for early development of MGT. Meticulous endoscopic inspection is especially important for the detection of MGT during the early follow-up period in patients with these initial tumor characteristics.
PubMed IF 2.8 소화기내과
1982017

제1저자 조은주 · 교신저자 김윤준

, , , , , ,
Current status and strategies for hepatitis B control in Korea.
Clin Mol Hepatol. 2017;23(3):205-211.

Abstract
Hepatitis B virus (HBV) infection is the most common cause of chronic liver diseases in Korea. After the introduction of the universal HBV vaccination program, the prevalence of hepatitis B surface antigen was markedly reduced, and Korea is now classified as an area of intermediate endemicity for HBV. However, there are still hurdles for elimination of hepatitis B, such as immunoprophylaxis failure against vertical transmission, occurrence of acute hepatitis B among peoples who did not have vaccination at younger age, and rapid increase of immigrant populations from HBV endemic areas. To achieve the World Health Organization goal of viral hepatitis elimination by 2030 in Korea, we suggest comprehensive policies for more effective control of hepatitis B as following: i) insurance coverage for antiviral prophylaxis in mothers with high viremia, ii) screening for hepatitis B seromarkers and catch-up HBV vaccinations of susceptible persons with hepatitis B, iii) establishment of an independent 'viral hepatitis sector' in Centers for Disease Control & Prevention to organize and execute comprehensive strategy for management of viral hepatitis, iv) encourage of management of HBV infection in immigrant populations, v) national campaign to promote awareness of hepatitis B.
PubMed IF 21.7 소화기내과
1972017

제1저자 황진호 · 교신저자 이정표

, , , , , , , , , ,
The prognostic significance of preoperative left ventricular diastolic dysfunction and left atrial enlargement on acute coronary syndrome in kidney transplantation.
Oncotarget. 2017;8(41):71154-71163.

Abstract
Echocardiography is commonly performed as a screening test to evaluate perioperative risks before kidney transplantation. However, only limited data are available on echocardiographic parameters of left ventricular diastolic dysfunction (LVDD) and left atrial enlargement (LAE) on acute coronary syndrome and mortality in kidney transplant recipients. We reviewed 2779 adult recipients who underwent pretransplant echocardiography from 1997 to 2012. We divided the patients into two and four groups by two categories: LVDD grades 0-1 vs. 2-3, and left atrial size quartile groups. During a mean follow-up of 4.5 years, acute coronary syndrome occurred in 89 (3.2%) patients. The recipients with LVDD grades 2-3 (P = 0.005 for non-fatal, P = 0.02 for fatal/non-fatal) and LAE (P = 0.001 for non-fatal, P = 0.03 for fatal/non-fatal) had a higher incidence of acute coronary syndrome after kidney transplantation. All-cause mortality did not differ significantly between the groups. In a multivariate analysis, LVDD of grades 2-3 (hazard ratio 2.98, 95% confidence interval 1.535-5.787; P = 0.001), and LAE (hazard ratio 1.052, 95% confidence interval 1.006-1.101; P = 0.03) were independently associated with non-fatal acute coronary syndrome. In patients who are kidney transplant candidates, pretransplant LVDD and LAE were independently associated with a higher incidence of acute coronary syndrome after kidney transplantation.
PubMed IF 5.168 신장내과
1962017

제1저자 송지현 · 교신저자 김상균

, , , ,
Risk Factors for Gastric Tumorigenesis in Underlying Gastric Mucosal Atrophy.
Gut Liver. 2017;11(5):612-619.

Abstract
BACKGROUND/AIMS Atrophic gastritis is considered a premalignant lesion. We aimed to evaluate the risk factors for gastric tumorigenesis in underlying mucosal atrophy.
METHODS A total of 10,185 subjects who underwent upper gastrointestinal endoscopy between 2003 and 2004 were enrolled in this retrospective cohort study. Follow-up endoscopy was performed between 2005 and 2014. Atrophic gastritis and intestinal metaplasia were assessed by endoscopy using the Kimura-Takemoto classification. Helicobacter pylori infection was evaluated based on serum immunoglobulin G antibody levels, the rapid urease test, or the urea breath test.
RESULTS Atrophic gastritis was confirmed in 3,714 patients at baseline; 2,144 patients were followed up for 6.9 years, and 1,138 exhibited increased atrophy. A total of 69 subjects were diagnosed with gastric neoplasm during follow-up (35 adenoma and 34 carcinoma). Age ≥55 years (hazard ratio [HR], 1.234), alcohol consumption (HR, 1.001), and H. pylori infection (HR, 1.580) were associated with increased mucosal atrophy. The risk factors for gastric neoplasm in underlying mucosal atrophy were age ≥55 years (HR, 2.582), alcohol consumption (HR, 1.003), extent of mucosal atrophy (HR, 2.285 in C3-O1; HR, 4.187 in O2-O3), and intestinal metaplasia (HR, 2.655).
CONCLUSIONS Extent of atrophy, intestinal metaplasia, and alcohol consumption are significant risk factors for gastric neoplasm in underlying mucosal atrophy.
PubMed IF 4.1 소화기내과
1952017

제1저자 이주명 · 교신저자 구본권

, , , ,
Physiologic mechanism of discordance between instantaneous wave-free ratio and fractional flow reserve: Insight from 13N-ammonium positron emission tomography.
Int J Cardiol. 2017;243:91-94.

Abstract
BACKGROUND Invasive physiologic indices, such as fractional flow reserve (FFR) or instantaneous wave-free ratio (iFR), are used in clinical practice. We sought to evaluate the physiological mechanism of discordance between iFR and FFR using ¹³N-ammonia positron emission tomography (PET)-derived quantitative parameters.
METHODS Data from 113 patients, who underwent both ¹³N-ammonia PET and invasive FFR and iFR measurement, were analyzed. Coronary circulatory indices, such as myocardial blood flow (MBF), coronary flow reserve (CFR), microvascular resistance, and trans-stenosis resistance were compared between patients with discordant results (low FFR despite high iFR) and those with concordant abnormal results (low FFR and low iFR), using cut-off values of FFR≤0.80 and iFR<0.90, respectively.
RESULTS Among the 113 patients, 39 (34.5%) showed concordant abnormal results in FFR and iFR measurement, and 17 (15.0%) showed discordant results between FFR and iFR (low FFR and high iFR). In comparison of coronary circulatory indices between discordant group and concordant abnormal group, both showed similar resting MBF (p=0.360), however, the discordant group showed higher hyperemic MBF and CFR, compared with the concordant abnormal group (p=0.003 and p<0.001, respectively). Trans-stenosis resistance was lower in the discordant group, in both resting and hyperemic status (p<0.001 for both). Although the discordant group showed higher resting microvascular resistance, these patients showed significantly higher reduction of microvascular resistance at hyperemia.
CONCLUSIONS Patients with low FFR despite high iFR showed significant differences in microvascular resistance, trans-stenosis resistance, absolute MBF, and CFR compared to those with concordant abnormal results between FFR and iFR.
PubMed IF 3.3 순환기내과
1942017

제1저자 이예진 · 교신저자 박종선

, , , , , , ,
Clinical impact of depression and anxiety in patients with idiopathic pulmonary fibrosis.
PLoS One. 2017;12(9):e0184300.

Abstract
BACKGROUND Although depression and anxiety represent significant yet treatable comorbidities in patients with idiopathic pulmonary fibrosis (IPF), their impact on the clinical course and prognosis of IPF remain unclear.
PURPOSE We investigated the prevalence and clinical significance of depression and anxiety in patients with IPF.
METHODS The present study included a prospective cohort comprising 112 Korean patients with IPF who had completed the Hospital Anxiety and Depression Scale (HADS) questionnaire.
RESULTS Symptoms of depression and anxiety were present in 25.9% and 21.4% of patients with IPF, respectively (HADS scores ≥8). No significant differences in demographic data, age, sex, smoking status, Modified Medical Research Council Dyspnea Scale (MMRC) scores, pulmonary function tests, or Gender-Age-Physiology Index for IPF were observed between patients with depression or anxiety and those without. However, in patients with anxiety, St. George's Respiratory Questionnaire (SGRQ) scores were significantly higher than those of patients without anxiety (40.5 versus 23.5; p = 0.003). The survival rate and total number of hospital admissions did not significantly differ between patients with depression/anxiety and those without.
CONCLUSIONS Our findings indicate that depression and anxiety are relatively common in patients with IPF. Although no significant differences were noted with regard to survival rate and hospitalization, the present study suggests that depression and anxiety significantly influence quality of life in patients with IPF.
PubMed IF 2.8 호흡기내과
1932017

제1저자 이준구 · 교신저자 김태민, 주영석

, , , , , , , , , , , , , , , , , , , , , ,
Clonal History and Genetic Predictors of Transformation Into Small-Cell Carcinomas From Lung Adenocarcinomas.
J Clin Oncol. 2017;35(26):3065-3074.

Abstract
Purpose Histologic transformation of EGFR mutant lung adenocarcinoma (LADC) into small-cell lung cancer (SCLC) has been described as one of the major resistant mechanisms for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, the molecular pathogenesis is still unclear. Methods We investigated 21 patients with advanced EGFR-mutant LADCs that were transformed into EGFR TKI-resistant SCLCs. Among them, whole genome sequencing was applied for nine tumors acquired at various time points from four patients to reconstruct their clonal evolutionary history and to detect genetic predictors for small-cell transformation. The findings were validated by immunohistochemistry in 210 lung cancer tissues. Results We identified that EGFR TKI-resistant LADCs and SCLCs share a common clonal origin and undergo branched evolutionary trajectories. The clonal divergence of SCLC ancestors from the LADC cells occurred before the first EGFR TKI treatments, and the complete inactivation of both RB1 and TP53 were observed from the early LADC stages in sequenced tumors. We extended the findings by immunohistochemistry in the early-stage LADC tissues of 75 patients treated with EGFR TKIs; inactivation of both Rb and p53 was strikingly more frequent in the small-cell-transformed group than in the nontransformed group (82% v 3%; odds ratio, 131; 95% CI, 19.9 to 859). Among patients registered in a predefined cohort (n = 65), an EGFR mutant LADC that harbored completely inactivated Rb and p53 had a 43× greater risk of small-cell transformation (relative risk, 42.8; 95% CI, 5.88 to 311). Branch-specific mutational signature analysis revealed that apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC)-induced hypermutation was frequent in the branches toward small-cell transformation. Conclusion EGFR TKI-resistant SCLCs are branched out early from the LADC clones that harbor completely inactivated RB1 and TP53. The evaluation of RB1 and TP53 status in EGFR TKI-treated LADCs is informative in predicting small-cell transformation.
PubMed IF 44.7 혈액종양내과
1922017

제1저자 서경진, 성지혜 · 교신저자 김진원

, , , , , , , , , , , , , , , ,
EGFR or HER2 inhibition modulates the tumor microenvironment by suppression of PD-L1 and cytokines release.
Oncotarget. 2017;8(38):63901-63910.

Abstract
BACKGROUND Characteristics of tumor microenvironment have been suggested as predictive markers of anti-EGFR or anti-HER2 treatment response. However, the effect of EGFR/HER2 signal blockade on the tumor immune microenvironment is unclear.
METHODS EGFR/HER2 pathway signaling and PD-L1 expression in gastric cancer cell lines were screened by western blot analysis. PD-L1 and HER2 expressions in 251 resected gastric tumors were determined by immunohistochemistry, and changes in EFGR, HER2, and PD-L1 expression in paired specimens between pre- and post-chemotherapy were evaluated. PD-L1 expression in HER2-amplified cell lines was evaluated by western blotting, fluorescence-activated cell sorting, reverse transcription, and real-time quantitative PCR analyses before and after afatinib, lapatinib, pictilisib and trametinib treatment. Changes in cytokines were evaluated by reverse transcription, real-time quantitative PCR, and enzyme-linked immunosorbent assay after EGFR/HER2 inhibition.
RESULTS Cell lines with pEGFR or pHER2 overexpression showed higher PD-L1 expression. In resected gastric tumors, HER2 expression was significantly associated with PD-L1 expression (p=0.030). PD-L1 overexpression accompanied by increased HER2 expression was identified in a post-chemotherapy specimen from a patient with an initial HER2/PD-L1-negative tumor. In HER2-overexpressing cell lines, PD-L1 expression was decreased in a dose- and time-dependent manner after afatinib and lapatinib treatment. PI3K pathway inhibition by pictilisib, but not MEK pathway inhibition by trametinib, resulted in PD-L1 suppression. After lapatinib treatment, the release of CCL2, CCL21, VEGF and CXCL1 decreased in a dose-dependent manner.
CONCLUSIONS Inhibition of the EGFR/HER2 signaling pathway, particularly of downstream PI3K activity, suppressed PD-L1 and release of cytokines, suggesting that EGFR/HER2 inhibition may create a more favorable milieu for tumor immunotherapy.
PubMed IF 5.168 혈액종양내과
1912017

제1저자 박주경, 백우현 · 교신저자 류지곤

, , , , , , ,
Additional K-ras mutation analysis and Plectin-1 staining improve the diagnostic accuracy of pancreatic solid mass in EUS-guided fine needle aspiration.
Oncotarget. 2017;8(38):64440-64448.

Abstract
BACKGROUND One of the major genetic alterations in pancreatic ductal adenocarcinoma (PDAC) is the point mutation of K-ras gene. Plectin-1 was also recently identified as PDAC specific biomarker. The aim of this study was to investigate the improvement of diagnostic accuracy of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) by using additional K-ras mutation analysis and Plectin-1 staining in patients with pancreatic mass.
METHODS A total of 85 study patients with pancreatic mass underwent EUS-FNA and the final diagnoses were as follows; PDACs: 70 patients, pancreas neuroendocrine tumor: 4, metastasis to pancreas: 5, autoimmune pancreatitis: 3, chronic pancreatitis: 1, tuberculous lymphadenitis: 1, pseudocyst: 1.
RESULTS Sensitivity, specificity and accuracy of pathologic diagnosis in EUS-FNA specimen were 81%, 80% and 79% accordingly. When we combine K-ras gene mutation analysis with histological assessment, we could get the following results for sensitivity, specificity and accuracy; cytology and K-ras mutation analysis: 93%, 87%, and 92%, cytology, K-ras mutation analysis, and Plectin-1 staining: 96%, 93%, and 95%.
CONCLUSIONS Triple combinations of the techniques; cytology, K-ras gene mutation analysis, Plectin-1 staining could increase accuracy in diagnosis of PDACs. Further investigation of using minimal specimens from EUS-FNA may give us insight to understand the biological behavior of PDAC.
PubMed IF 5.168 소화기내과
1902017

제1저자 정경연, 안화영 · 교신저자 문민경

, , , , ,
Association between thyroid function and lipid profiles, apolipoproteins, and high-density lipoprotein function.
J Clin Lipidol. 2017;11(6):1347-1353.

Abstract
BACKGROUND Thyroid hormone regulates lipid metabolism. In particular, it has been reported to regulate plasma high-density lipoprotein cholesterol (HDL-C) levels and the activity of molecules involved in HDL metabolism.
OBJECTIVE We investigated changes in the concentrations of lipids and apolipoproteins and in the function of HDL according to acute dynamic changes in thyroid function.
METHODS Concentrations of plasma lipids and apolipoproteins, paraoxonase-1 activity, and cholesterol efflux were measured in 27 patients with differentiated thyroid carcinoma who underwent total thyroidectomy and radioactive iodine (RAI) treatment, at 3 distinct times: After surgery (baseline subclinical hyperthyroid state), on the day of undergoing RAI treatment (overt hypothyroid state), and 3 months post-RAI treatment (subclinical hyperthyroid state).
RESULTS The mean free T4 and thyroid-stimulating hormone concentrations were 0.24 ± 0.06 ng/dL and 91.2 (77.8-118.2) μIU/mL, respectively, on the day of RAI treatment. Total cholesterol, triglyceride, low-density lipoprotein cholesterol, and apoB levels, and the apoA-I/II ratio were significantly increased in the overt hypothyroid state and recovered to baseline values with levothyroxine replacement. HDL-C and apoE levels were persistently elevated despite levothyroxine replacement. Paraoxonase-1 activity, corrected for apoA-I, decreased in the overt hypothyroid state but recovered with levothyroxine replacement (P = .009). Cholesterol efflux also decreased significantly in the overt hypothyroid state (21.5 ± 5.1% vs 18.9 ± 2.9%, P = .005), but remained low despite recovery of thyroid function.
CONCLUSION Changes in thyroid function are associated not only with changes in the concentrations of various plasma lipid components but also with changes in HDL function.
PubMed IF 6.9 내분비대사내과
1892017

제1저자 강혜린 · 교신저자 이연주

, , , , , , , , ,
A Comparative Analysis of Survival Prediction Using PRESERVE and RESP Scores.
Ann Thorac Surg. 2017;104(3):797-803.

Abstract
BACKGROUND Venovenous (VV) extracorporeal membrane oxygenation (ECMO) can be a life-saving therapy for patients with severe acute lung failure refractory to conventional therapy. The respiratory ECMO survival prediction (RESP) score and the predicting death for severe acute respiratory distress syndrome on VV-ECMO (PRESERVE) score were created to predict survival at the time of initiation of ECMO. This study aimed to validate both of these scores externally and to compare their predictive accuracies in patients with non-Western acute respiratory distress syndrome (ARDS).
METHODS In this retrospective cohort study, we reviewed and extracted data from electronic medical records of consecutive adult ARDS patients who were treated with VV-ECMO from 2007 to 2015. The PRESERVE and RESP scores were calculated for each patient. The outcomes of interest were inhospital and 6-month survival.
RESULTS In all, 99 patients were included. The mean age of the patients was 54 years, and male patients constituted 70% of the cohort. The inhospital and 6-month survival rates were 23% and 22%, respectively. Receiver-operating characteristics curve analysis of the PRESERVE and RESP scores showed area under the curve values of 0.64 and 0.69, respectively (p = 0.53), for inhospital survival. The receiver-operating characteristics areas under the curve for 6-month survival were 0.66 and 0.69, respectively (p = 0.68). The prognostic accuracies of the PRESERVE and RESP scores were thus similar.
CONCLUSIONS Both PRESERVE and RESP scores are useful for predicting survival in Asian ARDS patients, and both scores had similar prognostic accuracies in our Korean ARDS cohort.
PubMed IF 5.3 호흡기내과
1882017

제1저자 한승석 · 교신저자 나기영

, , , , ,
C-Reactive Protein Predicts Acute Kidney Injury and Death After Coronary Artery Bypass Grafting.
Ann Thorac Surg. 2017;104(3):804-810.

Abstract
BACKGROUND A better prediction of postoperative acute kidney injury (AKI) is worthwhile in patients undergoing coronary artery bypass grafting (CABG) because AKI is associated with high rates of morbidity and mortality. The present study was performed to investigate whether preoperative C-reactive protein (CRP) predicted AKI and the long-term rate of mortality in CABG.
METHODS This retrospective cohort study included 1,656 patients whose high-sensitivity CRPs were measured before CABG at two tertiary referral centers from 2004 to 2010. The odds ratios and hazard ratios for AKI and all-cause mortality were measured according to the tertiles of CRP levels after the adjustment of multiple covariates. The net reclassification improvement and integrated discrimination improvement were calculated to determine whether the addition of CRP to the risk model improves predictive capacity. Patients were followed for 12 years.
RESULTS The prevalence of AKI was increased in the third tertile group (42.7%) compared with in the first tertile group (25.6%). The corresponding odds ratio of AKI and p values were 1.86 (95% confidence interval: 1.39 to 2.49) and <0.001, respectively. Compared with the existing risk model, the addition of CRP improved the predictability with 0.135 of net reclassification improvement (p = 0.005) and 0.084 of integrated discrimination improvement (p < 0.001). There were 474 deaths (28.6%) during follow-up. The third tertile group exhibited a higher hazard ratio for mortality (1.63, 95% confidence interval: 1.27 to 2.08) than the first tertile group. This predictability for mortality remained consistent regardless of the presence of AKI.
CONCLUSIONS Preoperative CRP level is a predictor of postoperative AKI and mortality in patients undergoing CABG.
PubMed IF 5.3 신장내과
1872017

제1저자 송우정 · 교신저자 조상헌

, , , , , , , , , , , , , , ,
Diagnostic accuracy of fractional exhaled nitric oxide measurement in predicting cough-variant asthma and eosinophilic bronchitis in adults with chronic cough: A systematic review and meta-analysis.
J Allergy Clin Immunol. 2017;140(3):701-709.

Abstract
BACKGROUND Individual studies have suggested the utility of fractional exhaled nitric oxide (Feno) measurement in detecting cough-variant asthma (CVA) and eosinophilic bronchitis (EB) in patients with chronic cough.
OBJECTIVE We sought to obtain summary estimates of diagnostic test accuracy of Feno measurement in predicting CVA, EB, or both in adults with chronic cough.
METHODS Electronic databases were searched for studies published until January 2016, without language restriction. Cross-sectional studies that reported the diagnostic accuracy of Feno measurement for detecting CVA or EB were included. Risk of bias was assessed with Quality Assessment of Diagnostic Accuracy Studies 2. Random effects meta-analyses were performed to obtain summary estimates of the diagnostic accuracy of Feno measurement.
RESULTS A total of 15 studies involving 2187 adults with chronic cough were identified. Feno measurement had a moderate diagnostic accuracy in predicting CVA in patients with chronic cough, showing the summary area under the curve to be 0.87 (95% CI, 0.83-0.89). Specificity was higher and more consistent than sensitivity (0.85 [95% CI, 0.81-0.88] and 0.72 [95% CI, 0.61-0.81], respectively). However, in the nonasthmatic population with chronic cough, the diagnostic accuracy to predict EB was found to be relatively lower (summary area under the curve, 0.81 [95% CI, 0.77-0.84]), and specificity was inconsistent.
CONCLUSIONS The present meta-analyses indicated the diagnostic potential of Feno measurement as a rule-in test for detecting CVA in adult patients with chronic cough. However, Feno measurement may not be useful to predict EB in nonasthmatic subjects with chronic cough. These findings warrant further studies to validate the roles of Feno measurement in clinical practice of patients with chronic cough.
PubMed IF 11.2 알레르기내과
1862017

제1저자 최윤진 · 교신저자 김나영

, , , , , , , ,
Overlap between irritable bowel syndrome and functional dyspepsia including subtype analyses.
J Gastroenterol Hepatol. 2017;32(9):1553-1561.

Abstract
BACKGROUND AND AIM Coexistent gastrointestinal symptom profiles and prevalence or associated factors for the overlap between each functional dyspepsia (FD) and irritable bowel syndrome (IBS) group remain unclear. Thus, the aim of the present study was to evaluate the clinicodemographic features of FD, IBS, and IBS-FD overlap and assess the risk factors thereof, including subtype and genetic polymorphisms for IBS-FD.
METHODS Consecutive patients were enrolled from the outpatient Gastroenterology clinics of Bundang Seoul National University Hospitals in Korea. All gastrointestinal symptoms occurring at least once per week in the previous 3 months were recorded. Diagnostic criteria of functional gastrointestinal disorders were based on the Rome III criteria. Risk factors including genetic polymorphisms of 5-HTTLPR and ADRA2A 1291 G alleles and CCK-1R intron 779T>C were assessed using a multivariate logistic regression model.
RESULTS A total of 632 subjects (278 control subjects, 308 FD, 156 IBS, and 110 who met the criteria for both FD and IBS) were included in this study. Patients with IBS-FD overlap had more severe symptoms (such as bloating, nausea, vomiting, hard or lumpy stools, defecation straining, and a feeling of incomplete bowel movement) and higher depression scores compared with non-overlap patients. Single/divorced or widowed marital status, nausea, bloating, and a feeling of incomplete emptying after bowel movements were independent risk factors for IBS-FD overlap among IBS patients. In contrast, young age, depression, bloating, and postprandial distress syndrome were positively associated with IBS-FD overlap among FD patients. 5-HTTLPR L/L was a risk factor for the co-occurrence of IBS-C among FD patients (OR: 12.47; 95% CI: 2.00-77.75; P = 0.007).
CONCLUSIONS Bloating was a risk factor for IBS-FD overlap. Patients with postprandial distress syndrome have a higher risk of coexisting IBS, particularly constipation-dominant IBS.
PubMed IF 3.5 소화기내과
1852017

제1저자 윤도란 · 교신저자 김남중

, , , , , , , , , , , ,
Epidemiology and Clinical Characteristics of Zika Virus Infections Imported into Korea from March to October 2016.
J Korean Med Sci. 2017;32(9):1440-1444.

Abstract
Zika is a re-emerging, mosquito-borne viral infection, which has been recently shown to cause microcephaly and Guillain-Barré syndrome. Since 2015 the number of infected patients has increased significantly in South America. The purpose of this study was to identify the epidemiologic and clinical characteristics of patients with Zika virus (ZIKV) infections in Korea. Patients who had visited areas of risk and tested positive in the ZIKV reverse transcriptase polymerase chain reaction (RT-PCR) in blood, urine, or saliva specimens were included. The first Korean case of ZIKV infection was reported in March 2016, and 14 cases had been reported by October 2016. The median age of the patients was 34 years (19-64 years). Ten patients had been exposed in Southeast Asia and 4 in Latin America. Rash was the most common symptom (92.9%; 13/14), followed by myalgia (50.0%; 7/14), and arthralgia (28.6%, 4/14). There were no neurologic abnormalities and none of the patients was pregnant. Results of biochemical tests were normal. Positivity rates of RT-PCR for ZIKV in serum, urine, and saliva were 53.8%, 100.0%, and 83.3%, respectively in the first week of symptoms. In conclusion, 14 patients with ZIKV infections were reported in Korea by October 2016 and all of them had mild clinical symptoms.
PubMed IF 3.2 감염내과
1842017

제1저자 박찬순,박진주 · 교신저자 최동주

, , , , , , , , , , , , , ,
Relation of Renal Function with Left Ventricular Systolic Function and NT-proBNP Level and Its Prognostic Implication in Heart Failure with Preserved versus Reduced Ejection Fraction: an analysis from the Korean Heart Failure (KorHF) Registry.
Korean Circ J. 2017;47(5):727-741.

Abstract
BACKGROUND AND OBJECTIVES The relationship between ejection fraction (EF), N-terminal pro-brain natriuretic peptide (NT-proBNP) levels and renal function is unknown as stratified by heart failure (HF) type. We investigated their relation and the prognostic value of renal function in heart failure with preserved ejection fraction (HFpEF) vs. reduced ejection fraction (HFrEF).
MATERIALS AND METHODS NT-proBNP, glomerular filtration rate (GFR), and EF were obtained in 1,932 acute heart failure (AHF) patients. HFrEF was defined as EF<50%, and renal dysfunction as GFR<60 mL/min/1.73 m² (mild renal dysfunction: 30≤GFR<60 mL/min/1.73 m²; severe renal dysfunction: GFR<30 mL/min/1.73 m²). The primary outcome was 12-month all-cause death.
RESULTS There was an inverse correlation between GFR and log NT-proBNP level (r=-0.298, p<0.001), and between EF and log NT-proBNP (r=-0.238, p<0.001), but no correlation between EF and GFR (r=0.017, p=0.458). Interestingly, the prevalence of renal dysfunction did not differ between HFpEF and HFrEF (49% vs. 52%, p=0.210). Patients with renal dysfunction had higher 12-month mortality in both HFpEF (7.9% vs. 15.2%, log-rank p=0.008) and HFrEF (8.6% vs. 16.8%, log-rank p<0.001). Multivariate analysis showed severe renal dysfunction was an independent predictor of 12-month mortality (hazard ratio [HR], 2.08; 95% confidence interval [CI], 1.40-3.11). When stratified according to EF: the prognostic value of severe renal dysfunction was attenuated in HFpEF patients (HR, 1.46; 95% CI, 0.66-3.21) contrary to HFrEF patients (HR, 2.43; 95% CI, 1.52-3.89).
CONCLUSION In AHF patients, the prevalence of renal dysfunction did not differ between HFpEF and HFrEF patients. However, the prognostic value of renal dysfunction was attenuated in HFpEF patients.
PubMed IF 3.4 순환기내과
1832017

제1저자 원재경, 유수종, 황채영 · 교신저자 윤정환, 조광현

, , , , , , , , , , , , , , , ,
Protein disulfide isomerase inhibition synergistically enhances the efficacy of sorafenib for hepatocellular carcinoma.
Hepatology. 2017;66(3):855-868.

Abstract
UNLABELLED Sorafenib is the only approved targeted drug for hepatocellular carcinoma (HCC), but its effect on patients' survival gain is limited and varies over a wide range depending on pathogenetic conditions. Thus, enhancing the efficacy of sorafenib and finding a reliable predictive biomarker are crucial to achieve efficient control of HCCs. In this study, we utilized a systems approach by combining transcriptome analysis of the mRNA changes in HCC cell lines in response to sorafenib with network analysis to investigate the action and resistance mechanism of sorafenib. Gene list functional enrichment analysis and gene set enrichment analysis revealed that proteotoxic stress and apoptosis modules are activated in the presence of sorafenib. Further analysis of the endoplasmic reticulum stress network model, combined with in vitro experiments, showed that introducing an additional stress by treating the orally active protein disulfide isomerase (PDI) inhibitor (PACMA 31) can synergistically increase the efficacy of sorafenib in vitro and in vivo, which was confirmed using a mouse xenograft model. We also found that HCC patients with high PDI expression show resistance to sorafenib and poor clinical outcomes, compared to the low-PDI-expression group.
CONCLUSION These results suggest that PDI is a promising therapeutic target for enhancing the efficacy of sorafenib and can also be a biomarker for predicting sorafenib responsiveness. (Hepatology 2017;66:855-868).
PubMed IF 18 소화기내과
1822017

제1저자 이은봉 · 교신저자 이은봉

, , , , , ,
Effect of methotrexate discontinuation on efficacy of seasonal influenza vaccination in patients with rheumatoid arthritis: a randomised clinical trial.
Ann Rheum Dis. 2017;76(9):1559-1565.

Abstract
OBJECTIVE To investigate whether temporary discontinuation of methotrexate (MTX) improves the efficacy of seasonal influenza vaccination in patients with rheumatoid arthritis (RA).
METHODS In this prospective randomised parallel-group trial, patients with RA taking stable dose of MTX were randomly assigned at a ratio of 1:1:1:1 to continue MTX (group 1), suspend MTX for 4 weeks before vaccination (group 2), suspend MTX for 2 weeks before and 2 weeks after vaccination (group 3) or suspend MTX for 4 weeks after vaccination (group 4). All participants were vaccinated with trivalent influenza vaccine containing H1N1, H3N2 and B-Yamagata. The primary outcome was frequency of satisfactory vaccine response (≥4-fold titre increase 4 weeks postvaccination). Secondary endpoints included fold change in antibody titres from baseline.
RESULTS The per-protocol population consisted of 199 patients (n=54, 44, 49 and 52 in groups 1, 2, 3 and 4, respectively). Group 3 achieved higher satisfactory vaccine response against all three antigens than group 1 (51.0% vs 31.5%, p=0.044). The anti-H3N2 antibody fold increase (95% CI) was significantly higher in groups 3 and 4 (12.2 (8.4 to 17.5), p <0.001 and 10.0 (6.8 to 14.8), p=0.043, respectively) than group 1 (5.9 (4.3 to 8.1)). The anti-B-Yamagata antibody responses of groups 3 and 4 were higher (4.7 (3.3 to 6.7), p=0.048; 6.1 (4.2 to 8.8), p <0.001, respectively) than group 1 (2.9 (2.2 to 3.8)). RA flare occurred in 24.1%, 21.2%, 34.1% and 38.8% in groups 1, 2, 3 and 4, respectively (p=NS).
CONCLUSIONS Temporary MTX discontinuation improves the immunogenicity of seasonal influenza vaccination in patients with RA.
TRIAL REGISTRATION Trial registration number is: www.clinicaltrials.gov, NCT02748785.
PubMed IF 24 류마티스내과
1812017

제1저자 이태민 · 교신저자 최의근

, , , , , , , , , , , , ,
Increased Risk of Atrial Fibrillation and Thromboembolism in Patients with Severe Psoriasis: a Nationwide Population-based Study.
Sci Rep. 2017;7(1):9973.

Abstract
Psoriasis increases the risk of atrial fibrillation (AF) and thromboembolic events (TE). There is limited information on the effect of psoriasis severity on AF and TE. In this study, psoriasis patients were enrolled from the Korean National Insurance Service-National Sample Cohort (2004-2008). Diagnosis and disease severity were determined from claims data. Newly diagnosed non-valvular AF and TE were identified during a 9.6-year follow-up. The effect of psoriasis severity on AF and TE was evaluated. We identified 13,385 psoriasis patients (1,947 with severe psoriasis). Severe psoriasis significantly increased the risk of AF (adjusted hazard ratio [HR_adjust] 1.44 [95% confidence interval (CI) 1.14-1.82], p = 0.002) and TE (HR_adjust 1.26 [95% CI 1.07-1.47], p = 0.005); mild psoriasis did not show any significant effects. Results were similar after propensity-score matching. Risk increments of AF and TE were prominent in patients with greater cardiovascular risk. A possible limitation of our study is that it has a retrospective design, and the effect of unmeasured confounders and risk of misclassification could bias the results. To conclude, our results showed that severe, but not mild, psoriasis significantly increased AF and TE risk. AF surveillance and active stroke prevention would be beneficial in such cases.
PubMed IF 4.9 순환기내과
1802017

제1저자 김학령 · 교신저자 김명아

, , , , , , , , , , , , , , , , , ,
Gender Difference in the Prognostic Value of N-Terminal Pro-B Type Natriuretic Peptide in Patients With Heart Failure - A Report From the Korean Heart Failure Registry (KorHF).
Circ J. 2017;81(9):1329-1336.

Abstract
BACKGROUND Very little data is available to evaluate the gender-specific role of N-terminal pro-B type natriuretic peptide (NT-proBNP). This study was performed to investigate whether there is a gender difference in the prognostic value of NT-proBNP in patients hospitalized for heart failure (HF).
METHODS AND RESULTS A total of 2,280 patients hospitalized with HF (67.9±14.3 years, 50.9% women) from the nationwide registry database were analyzed. Composite events including all-cause mortality and HF readmission were assessed. During the mean follow-up period of 1,245±824 days, there were 1,067 cases of composite events (49.7%). NT-proBNP levels were significantly higher in patients with events than those without in both genders (P<0.001 for each). A higher NT-proBNP level was an independent predictor of events (highest vs. lowest tertile: hazard ratio [HR], 1.74; 95% confidence interval [CI], 1.25-2.43; P=0.001) in men, even after controlling for potential confounders. However, NT-proBNP was not associated with the occurrence of composite events in women in the same multivariable analysis (P>0.05).
CONCLUSIONS In patients with HF, the NT-proBNP level seems to be a more valuable marker in the prediction of long-term mortality and HF readmission in men than in women.
PubMed IF 5.8 순환기내과

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